IMMUNOTOXICITY OF INVITRO VANADIUM EXPOSURES - EFFECTS ON INTERLEUKIN-1, TUMOR-NECROSIS-FACTOR-ALPHA, AND PROSTAGLANDIN-E2 PRODUCTION BY WEHI-3 MACROPHAGES

Treatment of cultured mouse macrophages with either of two different v anadium compounds was shown to affect the production/release of two ma jor immunoregulatory cytokines. The pentavalent vanadium compound ammo nium metavanadate was shown previously to disrupt cell-mediated immuni ty at the earliest stages of an in vivo anti-Listerial response, in th at mice treated with vanadium displayed decreased accessory cell recru itment and numbers of activated macrophages at infection sites. To det ermine whether these effects were due to vanadium-induced alterations in the production of biologically-active mediators, mouse macrophage-l ike WEHI-3 cells were treated in vitro with ammonium metavanadate or v anadium pentoxide prior to stimulation with lipopolysaccharide endotox in (LPS). After stimulation, monokine (tumor necrosis factor-alpha and interleukin-1) and prostaglandin E2 (PGE2) activities were assessed. Both vanadium compounds decreased recovered monokine activities; measu red TNFalpha concentrations were also reduced. Spontaneous release of the IL-1/TNF-regulating prostanoid PGE2 was significantly increased by the highest concentration of vanadate tested, although LPS-stimulated PGE2 production was unaffected by either compound. These results indi cate that, in vitro, pentavalent vanadium can interfere with immunoreg ulatory mediators critical for maintaining host immunocompetence.